Neurologic and neuropsychiatric disorders such as depression, anxiety, amyotrophic lateral sclerosis, and central nervous system injuries, to name a few, afflict millions of people every year resulting in a multitude of symptoms including weight change, decreased energy, headaches, digestive problems, chronic pain, paralysis, and in certain instances, death.
One class of growth factors proposed as a treatment for neurologic and neuropsychiatric disorders are neurotrophins, which include brain-derived neurotrophic factor (BDNF). BDNF is believed to have neurotrophic action on various neuronal populations including sensory neurons, motor neurons, dopaminergic neurons of the substantia nigra, and cholinergic neurons of the basal forebrain, which are involved in several neurologic and neuropsychiatric disorders. Preclinical evidence indicates that BDNF might be useful as a therapeutic agent for various neurologic and neuropsychiatric disorders; however, the in vivo instability of such a peptide therapy limits its usefulness.
Neurotrophins are also indicated in metabolic disorders. Mutations in the tyrosine kinase receptor trkB or in one of its natural ligands, e.g., BDNF or neurotrophin-4 (NT4), are known to lead to severe hyperphagia and obesity in rodents and humans. Administration of trkB ligands such as BDNF or NT4 have been shown to suppress appetite and body weight in a dose-dependent manner in several murine models of obesity. Accumulating evidence indicates that TrkB signaling directly modulates appetite, metabolism, and taste preference. TrkB agonists thus emerge as potential therapeutics for metabolic disorders.